Scientists and clinicians still have a lot to learn about how sex differences impact human diseases, such as how they can cause variations in symptoms, outcomes, and treatment efficacy. To shed some light on this mysterious topic, researchers compared the expression of proteins in males and females, and in hundreds of disease states, using data from the UK Biobank. The findings have been reported in Nature Communications.
This study analyzed the levels of around 5,800 proteins in human plasma in over 30,000 females and over 26,000 males. This showed that the levels of about two-thirds of those proteins differ significantly depending on sex.
However, the genetic effects on these proteins were largely similar.There was a small group of about 100 proteins of the 5,800 studied whose levels were controlled by genetics, and which depended on sex.
But this research has suggested that differences in the levels of many proteins between males and females are not due to genetics but instead, happen because of other factors such as hormones, lifestyle, financial state, and geography - like where people work and live. When considering differences that are seen in males and females in diseases or the effects of medications, for example, scientists should look beyond genetics to many other things.
"Our findings highlight the need to better understand the factors that impact health difference at the genetic level and beyond to create more tailored and equitable health care for everyone," said first study author Mine Koprulu, Ph.D., a postdoctoral researcher at Queen Mary University of London's Precision Healthcare University Research Institute (PHURI).
Data on genetic differences in protein expression and function are often incorporated into drug development pipelines. "From this perspective, better understanding of population differences in the regulation of proteins, such as those between males and females, is essential to guide precision medicine approaches and identify where one size may not fit all," noted Professor Claudia Langenberg, Director of the PHURI, among other appointments.
The data in this study categorized males and females based on chromosomes, like carriers of XX or XY, which the authors acknowledge is not always the same as a person's gender identity. But such generalized categorizations are sometimes required for a large scientific study on population-level differences. Gender identity was also not always included for each individual, and was not consistently available.
Sources: Queen Mary, University of London; Nature Communications